Discovers that cells actively create
heterogeneity in LDs, with some cells having few LDs and some having
many. This decreases overall ROS, and the high-lipid cells can supply
lipids to the low-lipid cells when needed.

Uses an improved minimization approach to better
implement maximization of Q, resulting in improved community detection.
This is applied to protein-interaction networks, and the resulting
detected communities are then used as additional information in
predicting protein function.

Discovers what we believe to be a new pathway in
innate immunity, where anti-bacterial histone proteins are sequestered
on cytoplasmic lipid droplets, and then released in the presence of
cytosolic bacteria, to kill the invaders. Please also see the
accompanying "insight" article by Roberto Kolter:[pdf]

Shows that for multiple-motor based transport,
velocity can be used to control mean travel. For single kinesin motors,
processivity is independent of velocity, which means that the slower
you go, the lower the single-motor off rate. Thus, for multiple motors
acting together, since the "on" rate is independent of velocity, but
the off-rate is not,?the ratio of on-rate to off-rate can be tuned by
velocity, and this can be used to quite dramatically alter how far the
group of motors takes the cargo.

Discovers a new pathway of kinesin
inactivation/reactivation. Shows that kinesin by itself tends to go
inactive, and that this inactivation can be reversed by the presence of
CK2, both in vitro and in vivo. Importantly, this new
inactivation/reactivation pathway does NOT involve autoinhibition of
kinesin via the established head-tail inactivation pathway, as even
tail-less kinesin goes inactive.

A paper following-up on the in-vitro study (#53,
below) of Dynein"s regulation by NudE and Lis1, but this time looking
at transport in cells. The main points are 2. First, that coordination
between opposite motors (for bi-directionally moving transport) is NOT
directly and immediately mediated by activity of the motors. That is,
when dynein (minus-end) activity is decreased rapidly (by acute
inhibition), plus-end motion is inhibited, but with a temporal delay.
Thus, however motor inactivation is sensed (potentially by force
production, or other mechanisms), once detected, inactivation of the
opposite motors requires some additional feedback mechanism. This is
consistent with the fact that in vitro, neither kinesin or dynein
require opposite-polarity motors to be present to function. The second
point of the paper is that in neurons, larger cargos appear likely to
be exposed to significantly more opposition to motion, so that their
appropriate transport requires NudE/Lis1 function, but this?requirement
is much less for smaller cargos.

?A short review/opinion piece with a bit of new
data, furthering the idea presented in #56 below, i.e. that that loss
of CAV1 function can result in multiple disease phenotypes by affecting
Mitochondrial function, in particular by altering cholesterol in the
mitochondrial membrane.

Discovers that loss of CAV1 function can result
in multiple disease phenotypes by affecting Mitochondrial function.
CAV1 is discovered to contribute to mitochondrial cholesterol
homeostasis, and by altering cholesterol in the mitochondrial
membrane,?loss of CAV1 function thus results in a variety of
alterations of mitochondrial function.

2010

Determines the mechanistic effects of the LOA
mutation, a mutation in the dynein heavy chain, that leads to an
ALS-like phenotype in heterozygous mice bearing the mutation.
Homozygous mice die at birth. The paper has a number of main findings.
First, that the mutation decreases single-molecule processivity.
Second, that this defect carries over to multiple-motor transport, and
the effects on processivity at the single-molecule can quantitatively
explain?the observed impairment in multiple-motor based transport,
likely resulting in the observed disease phenotype. This study thus
provided the first direct experimental evidence supporting the
long=hypothesized importance of single-motor processivity for healthy
transport. The study also suggests a role for the tail in controlling
enzymatic coordination between the two heads. Because this loss of
enzymatic coordination correlates with increased side-to-side stepping
of the motor, and hence less lateral contact between the two heads, we
believe this is consistent with a mechanism whereby dynein heads
communicate with each other laterally.

Discovers the mechanistic role of NudE and Lis1.
Briefly, NudE alone both recruits dynein to a particular location, but
also inactivates it. Lis1 then binds NudE, and the combined
Dynein-NudE-Lis1 complex is again active, but now with improved
performance. In particular, the complexes processivity is increased,
and more importantly, detachment under load is decreased. This allows
the motors to "hold on" under load, and is critical in allowing
multiple motors to work well together. In the presence of NudE and
Lis1, the same number of motors can exert a higher average force, not
because each motor exerts more force, but rather because on average
more motors are engaged (they don"t fall off).

Investigates theoretically how multiple kinesin
motors function together, and how uneven load sharing can result in
enhances system performance under load. It finds that ensemble multiple
motor function depends strongly on the coupling between the motors. It
predicts"which is then confirmed experimentally"that surprisingly, for
a range of likely cytosolic viscosities, cargos driven by a single
motor can move faster than cargos moved by two or more motors.

A brief review discussing a paper from the
Lipowsky group that recently appeared in PNAS. The work is very
intriguing, in that it presents a model that suggests that many aspects
of bi-directional vesicular motion may be explained quantitatively due
to specific properties of single motors, and how tug-of-wars are
resolved.?/blockquote>

A previous PNAS paper (#38, below) investigated
how two or three kinesin motors function together, and showed that
tau"at levels found in cells"can function to regulate the number of
engaged motors, allowing cells the possibility to spatially regulate
plus-end transport via control of track (microtubule) accessibility.
This raised the potential problem of cross-talk between plus-end and
minus-end transport, since they both occur along microtubules. In this
manuscript we investigate dynein"s sensitivity to tau, in both the
single- and multiple-motor regimes. We show that filament-level
regulation can occur without cross-talk, because dynein is essentially
unaffected by the low levels to moderate levels to tau that so
significantly alter kinesin-based transport. Using a construct (a
portions of dynein"s microtubule-binding domain), we investigate how
dynein avoids kinesins" tau sensitivity.

Investigates properties of different
step-detection methods, and then applies the best one to the problem of
how multiple kinesin motors function together. It shows that under low
load, and saturating ATP, in vitro two kinesin motors attached to a
cargo do not coordinate, but instead function independently, so that
the center of mass of the cargo moves in ~4nm steps.

2007

A review of advances in our understanding of how
multiple motors move cargos, and the ramifications of the number of
engaged motors moving cargos. Based on a summary of structural (EM
data) and in vivo force measurements, it suggests that most cargos
transported along microtubules are moved by a limited number of motors
(between 1 and 5).

A brief review of advances in myosin V-actin
filament-filament switching, discussing both the role of the number of
motors on the cargo, and also new results on the properties of single
Myosin-V motors.

Investigates how two or three kinesin motors
function together, and shows that stall forces for motors are additive,
and that multiple kinesin motors move cargos very long distances. It
then shows that tau"at levels found in cells"can function to regulate
the number of engaged motors, allowing cells the possibility to
spatially regulate transport via control of track (microtubule)
accessibility.

Investigates, both theoretically and
experimentally, the published proposal that a cargo"s velocity can be
used to infer the number of engaged motors moving the cargo. The
manuscript concludes that cargo velocity is likely a poor marker for
the number of engaged motors.

Investigates how two or three kinesin motors
function together, and shows that stall forces for motors are additive,
and that multiple kinesin motors move cargos very long distances. It
then shows that tau"at levels found in cells"can function to regulate
the number of engaged motors, allowing cells the possibility to
spatially regulate transport via control of track (microtubule)
accessibility.

2006

R. Mallik and S. P. Gross,?"Molecular motors as cargo
transporters in the cell "The good, the bad and the ugly",?Physica A,
V. 372,?65 "69, (2006). [pdf]

Uses mass spectrometry to determine the proteins
present on embryonic lipid droplets.?Because the proteins present are
found to be highly conserved between Drosophila and mammalian droplets,
this suggests that studying the Drosophila droplets can provide
important insights into the similar processes in mammals. In the
proteome, certain unexpected proteins"histones"are present in large
amounts The localization of histones to the droplets is investigated in
depth, and concluded to be real, and temporally regulated. Based on
these findings, together with published observations from others, the
manuscript proposes a new model for lipid droplets as generalized sites
of protein storage/sequestration.

Investigates how two or three dynein motors
function together, and shows that stall forces for motors are additive,
and that multiple dynein motors move cargos very long distances. Shows
that a cargo moved by two dyneins is expected to move a very long
distance, so that for cargos moved by two or more dynein motors in
cells, the dynactin complex (which increases dynein processivity) is
likely unnecessary as far as facilitating travel distance. This does
not?mean, however, that the dynactin complex is unimportant"we have
previously shown that in some cases it plays a role in coordinating
kinesin and dynein, and others have shown that it frequently plays an
important role in dynein-cargo attachment.